A biophysical model predicts 3D cellular connectivity

An international team of scientists, led by the Institute of Biomedicine of Seville (Ibisa joint center of the Virgen del Rocío University Hospital, the CSIC and the University of Seville) and the Institute of Biology of Integrative Systems (I2SysBiofrom the University of Valencia and the CSIC), discovered a new mathematical principle and developed a biophysical model that help explain how some cells connect with each other to form tissues.

The study, published in the journal Cell Systems, was made using the fruit fly as a model, and may have future implications for the creation of artificial tissues and organs in the laboratory. It could also serve to better understand how organs are formed during embryonic development and the pathologies associated with this process.

Although, for the time being, work has focused on the epithelial cells tubular, and the results reveal that they have apical and basal intercalations that minimize energy. Taking this into account, the authors developed an energy-based biophysical model capable of predict cellular connectivity in 3D.

Biophysical model and three-dimensional predictions raised by the researchers. / P. Gómez-Gálvez et al./Cell Systems

This same team of scientists published in 2018 in the journal Nature Communications an article of great scientific and media repercussion, in which they demonstrated that epithelial cells can adopt a geometric shape during the formation of previously undescribed organs: the scutoid.

“That cells adopt this geometric shape is due to the energy savings that this entails by ‘packing’ to form tissues when there is a certain level of curvature (for example, when a fold forms in a tissue). Our research represented an important paradigm shift, as until then epithelia had always been studied using mathematical concepts to describe their organization in two dimensions, something that is related to the connection between cells and how they communicate with each other to form these organs correctly. ”. explains one of the authors leading this work, Luisma EscuderoIBIS researcher.

We have developed a biophysical model that relates tissue geometry and the physical properties of cells for the first time to how they are connected to each other.

Luisma Escudero (IBIS)

“However, as we showed at the time, epithelial cells can have complex 3D shapes, such as scutoids, and cells and organs are also three-dimensional. Therefore, in this article we consider whether there are 3D mathematical and/or biophysical principles and, by combining experiments with fly tissue and computer models of tubular tissue, we were able to develop a biophysical model that, for the first time, relates tissue geometry and the physical properties of cells to how they are connected to each other. ”, highlights Escudero.

The key is the ‘social relationships’ of the cells

Javier Pussy, a researcher at I2SysBio and co-leader of the study, establishes a simile to explain this new scientific advance, using Anthropology. “Anthropologist Robin Dunbar has determined that humans have an average of five close friends that are given by different social and personal factors. At the cellular level, our paper revealed that there is an “equivalent” principle, concluding that the number of a cell’s close ‘neighbors’ (i.e. its ‘close friends’) is determined in this case by the tissue geometry and its energetic relationships.

The number of a cell’s close ‘neighbors’ (i.e. its ‘close friends’) is determined in this case by the tissue geometry and its energy relationships

Javier Buceta (I2SysBio)

“Thus, taking into account a number of energetic, biological and geometric considerations, we found that, for example, the more connections an epithelial cell has with other cells, the more energy it needs to establish new connections with other cells, whereas, if it is poorly connected with other ‘neighbors’, the cell needs less energy to establish this connection”, highlights Buceta.

In this research, scientists changed the fabric, reducing adhesion between cells to test your model. “This causes the organization to change, as it is easier (energy-speaking cheaper) for cells to come into contact with new cells,” says Buceta. The results of experiments confirmed the quantitative principle proposed by the researchers.

The geometry of the scutoids determines cell connectivity

The authors point out that, analyzing the behavior of tissues from the point of view of materials, other previous works have observed that their “stiffness” depends on cellular connectivity. “In this way, tissues can behave more or less viscously (that is, more fluid or more solid). Our results quantitatively show how the geometry of scutoids determines cell connectivity and, therefore, how they can be biological instrument regulate the properties, such as material, of tissues and organs”, conclude Escudero and Buceta.

In addition to the researchers from IBiS and I2SysBio, others from the University of Seville, the Johns Hopkins University in the United States and the University of the Basque Country, among other institutions, participated in this work.